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t(11;14)-positive clones can persist over a long period of time in the peripheral blood of healthy individuals

Leukemia volume 23, pages 1190–1193 (2009)Cite this article

Several lymphoma- and leukaemia-associated chromosomal translocations are present in the peripheral blood of healthy individuals (HI). Translocation t(14;18), the genetic hallmark of follicular lymphoma (FL) that juxtaposes the BCL2 proto-oncogene near the immunoglobulin heavy chain (IGH) locus, can be detected in most HI at highly variable frequency.1 Individual characteristics, such as smoking habits, viral infection, and occupational and/or environmental factors (such as pesticide exposure), suspected to play a role in lymphoma genesis, have been associated with an increase in t(14;18) translocation frequency.2 We recently showed that clonotypic t(14;18)-positive cells can persist in the peripheral blood over a long period of time.3 High t(14;18) rates in HI are mainly because of an expanding population of atypical B cells issued from germinal centre that share genotypic and phenotypic features with FL cells.4 t(14;18)-positive cells in HI may thus represent much more advanced precursors of the FL pathway than thought earlier.

As t(14;18) in FL, translocation t(11;14)(q13;q32) is considered as the primary event in the pathogenesis of mantle cell lymphoma (MCL), a neoplasia that accounts for 5–10% of all non-Hodgkin's lymphoma.5 The juxtaposition of the immunoglobulin heavy chain joining region on chromosome 14 to a chromosomal locus on 11q13 places the CCND1/BCL1 gene under the control of the IGH enhancer, resulting in aberrant overexpression of cyclin D1, a positive regulator of the cell cycle.5 Both t(11;14) and t(14;18) translocations are thought to arise from the same mechanism of illegitimate repair of V(D)J recombination intermediates, with recombinase-mediated breaks in the IGH locus and double-stranded breaks of different origins at the oncogene loci.6 Considering mechanistic and oncogenic similarities between t(14;18) and t(11;14), we sought to evaluate the incidence of t(11;14) in HI and their persistence over time. To date, the presence of t(11;14)-positive cells in peripheral blood from HI has only been reported in one individual over the hundred HI studied and at a relatively low frequency (∼six copies in 1 million normal cells).7

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Acknowledgements

We would like to thank nurses from the centralized unit of blood sampling (Centre François Baclesse). We are grateful to Dr Véronique Salaün (Hématologie Biologique, CHU Côte de Nacre, Caen) and Dr Dominique Vaur (Biologie clinique oncologique, Centre François Baclesse) for providing blood samples from MCL patients. This work was supported by grants from the Ligue Nationale contre le Cancer (Comité de la Manche), Association pour la Recherche sur le Cancer (ARC), Conseil Général du Calvados, Union des Industries de la Protection des Plantes and the Fondation Weisbren-Benenson.

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  1. Groupe Régional d'Etudes sur le Cancer, IFR146 ICORE, Université de CAEN Basse-Normandie, CLCC François Baclesse, Caen, France

    Y Lecluse, P Lebailly, A-C Gac & P Gauduchon

  2. Registre général des tumeurs du Calvados, CLCC François Baclesse, Caen, France

    P Lebailly

  3. Laboratory Genomic Instability and Human Hemopathies, Centre d'Immunologie de Marseille-Luminy (CIML), CNRS-INSERM-Université de la Méditerranée, Marseille, France

    S Roulland & B Nadel

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  1. Y Lecluse
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  2. P Lebailly
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  5. B Nadel
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  6. P Gauduchon
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Correspondence to P Gauduchon.

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Lecluse, Y., Lebailly, P., Roulland, S. et al. t(11;14)-positive clones can persist over a long period of time in the peripheral blood of healthy individuals. Leukemia 23, 1190–1193 (2009). https://doi.org/10.1038/leu.2009.31

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